Wino115 wrote:
This won't make anyone happy, but I will voice what is probably the frustration we all feel. So I am subscribed to Barclays biotech research and they have a massive research team looking at all sorts of cutting edge biotechs. One guy specializes in oncology (Peter Lawson) with a PhD from Cambridge or something like that. He digs into the science to try to find drugs he thinks have at least a decent shot at working. I read stuff about unbelievably complex approaches to targeting tumors and selectively "turning on" your drug, altering the immune system to work better, etc. it almost seems the more far-fetched the complexity is, the more attention the company gets. But they cover these and value them and recommend them to their client base. He looks at all these crazy early science companies along with some simpler ones with a high probability of success.
Yet here we see in JFMs well written description that I've highlighted below, the straight forward science of what they are doing and why it may work really well. Yes, it's ground-breaking and complex, but nothing like some of the highly experimental and rube Goldberg like descriptions of some of the approaches I see and that analysts cover. I just don't get why someone who understands oncology and can read the key 3-4 papers would not want to at least understand this drug, what it's doing, how it's doing it, why there is proven scientific rationale for it to work, and what it could mean for a $350mil company. I just don't get why no one wants to understand it in its comparative simplicity. Of all the many approaches I've tried to understand, this is definitely on the simpler side of things. Soleus's other investment (Bioatla) is wildly complex compared to THTX. Read this description of their approach compared to SORT1, it's crazy risky comparatively:
"BioAtla scientists have discovered a novel chemical switch mechanism involving physiological-occurring chemicals, such as bicarbonate and hydrogen sulfide. These molecules are negatively charged at physiological conditions and interact with positive charged areas on the protein surface. Under acidic conditions of the tumor microenvironment they are neutralized and released from the protein surface, uniquely allowing CAB antibodies to bind to their target and attack the tumor cell. BioAtla refers to this novel physiological mechanism, used for generating CABs, as Protein-associated Chemical Switch(es) or PaCS Mechanism."
Yet this is followed and liked by analysts and investors. Think of all the things that could go wrong with that! So that is what is most frustrating is that TH1902 is straight forward compared to many other approaches, yet the specialist biotech analysts are completely unaware of it for the most part and either aren't excited by the science, don't see the quid pro quo coming, or haven't bothered to learn about it. Getting past P1 will change all that, I know. But not having at least a few analysts look under the hood now is very frustrating given some of the science they do spend time on.
The one thing I do see is that of all the companies a firm like Barclays cover, most have at least one cancer product in either P2, P3 or commercialized. So I get that, but they do have some with pre clinical and P1 covered as well.
jfm1330 wrote: I think we now have the proof that the last financing was unavoidable at terms similar to what was done. The market is simply unwilling to give them the benefit of the doubt on anything. They will swallow cr*p from other companies, but Thera is clearly on the black list of most. The market is very reluctant to give them credit for anything, but with real positive hard data on humans, some will change their minds and will recognize the reality. But it is quite clear now that we still have to wait a few months to see the beginning of that process.
The presentation yeserday was excellent, and the non verbal part was very telling in my view. These guys know more than us and they are very confident. Marsolais said that they were close to the MTD of free docetaxel, and if there is no neutropenia at all at that point, it will not happen drastically at the next higher dose. Toxicity appears gradually with dose increases. All that to say that they are already convinced that TH1902 MTD will be much higher than the MTD of docetaxel. They are convinced of that. They know it is the way it looks right now, but they still need to prove it. A much higher MTD would be a very strong signal of probable efficacy.
Again. Go back to the Q&A part of the presentation and look at their faces when asked if TH1902 would work better the more a cancer is at an advanced stage. They smile, but at the same time they try not to smile too much. They are convinced that they have something special in their hands because the combination of the features of the PDC and the target (sortilin) is so great. A small peptide with very high loading capacity while retaing affinity to sortilin with a selectively cleavable linker. The ideal target, sortilin, a membrane receptor whose role is to import/export large molecules through the cellular membrane by way of endocytosis, which allows to bypass a resistance mechanism to docetaxel, and the best part is the expression of sortilin is very low in all healthy tissues, except the neurones, but TH1902 does not cross the blood brain barrier, and the expression is high in many cancers, and increases as the cancer evolves to a more agressive stage. Really the perfect target to treat refractory advanced cancers. Obviously, not all cancer are expressing sortilin, but the percentage of them that do express it represents an enormous part of all cancers, so an gigantic potential market. If it would succeed with only 10% of that, it would still be a blockbuster platform, because, again, the real value is not only in TH1902, but in the peptide (TH19P01) that can be loaded with any cytotoxic agent. Marsolais said it verbatim yesterday.
In a way I am back to my "too good to be true" that I was repeating about the ibalizumab deal a few years ago. In the end, ibalizumab (Trogarzo) ended up as a commercial failure, but there was a window of opportunity to make a lot of money with it. I was dumb enough to miss it, like many others here that are now very frustrated because of that. But now we are up for another opportunity. I am quite convinced it will be really good. How good? I am not sure, but good enough. That being said, it seems the market still believes that it looks too good to be true, and the Trogarzo fiasco is probably an explaination as to why there is so much skepticism. But reality always catch up and the answer is becomes clear.